Vasopressin in Traumatic Hemorrhagic Shock Study

A Multicenter, Randomized, Controlled Trial Assessing Arginine Vasopressin Versus Saline Placebo in Refractory Traumatic Hemorrhagic Shock Patients (VITRIS-study)

The purpose of the present trial is therefore to assess effects of arginine vasopressin vs. saline placebo on hospital admission rate (primary end point), as well as hemodynamic variables, fluid resuscitation requirements and hospital discharge rate (secondary study end points) in presumed traumatic hemorrhagic shock patients with a systolic arterial blood pressure <90 mm Hg after 10 min of standard shock treatment. Accordingly, the study reflects an add-on design to standard traumatic shock therapy.

The hypothesis is that both arginine vasopressin and saline placebo have comparable effects on hemodynamic variables, fluid resuscitation requirements, and hospital admission and discharge rate. The alternative hypothesis is that arginine vasopressin has more beneficial effects on hemodynamic variables, fluid resuscitation requirements, and hospital admission and discharge rate than saline placebo.

Study Overview

• Status: Completed
• Conditions: Shock; Hemorrhagic Shock; Hypovolemia
• Intervention / Treatment: Drug: Vasopressin; Drug: Saline placebo

Detailed Description

The study will be designed as a multicenter, randomized, placebo-controlled clinical trial with blinded assessment of the outcome in a study network with helicopter emergency medical service units in Austria, Germany, Switzerland, Italy, Czech Republic and the Netherlands.

The protocol, information and consent procedure will be approved by the institutional review board of each participating center. Since this is a study randomizing unconscious patients who are unable to give informed consent at the time of randomization (§43a Emergency study), the requirement of informed consent is planned to be waived in accordance with the ethical standards of national legislation in Germany, Austria, Switzerland, Italy, Czech Republic and the Netherlands and the guidelines for good clinical practice of the European Agency for the Evaluation of Medicinal products. Depending on the patient's outcome, either the surviving patient, or the patient's family in case of death of the patient or in case that the patient survives but remains mentally handicapped will be informed about the trial (see appendix for patient information sheet); the protocol specifies that if there are any objections, the patient will be withdrawn from the study.

Treatment assignments of blinded study drugs will be randomly generated by computer in blocks of two, with stratification according to center. Before the start of the trial, staff at participating centers will be informed about the rationale of the protocol and the study; participating centers will be subsequently contacted and visited to ensure proper enrollment.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, A-5020
    • Hospital Salzburg
  • Lower Austria
    • Amstetten, Lower Austria, Austria, A-3300
      • HEMS Ybbsitz / Hospital Amstetten
    • Krems, Lower Austria, Austria, A-3500
      • Hospital Krems
    • Wiener Neustadt, Lower Austria, Austria, A-2700
      • Hospital Wiener Neustadt
  • Styria
    • Graz, Styria, Austria, A-8036
      • Medical University of Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, A-6020
      • Medical University of Innsbruck
  • Upper Austria
    • Linz, Upper Austria, Austria, A-4021
      • Hospital Linz
    • Schaerding, Upper Austria, Austria, A-4780
      • HEMS Suben / Landeskrankenhaus Schärding
• Germany
  • Dresden, Germany, D-01307
    • University Hospital of Dresden
  • Goettingen, Germany, D-37075
    • University Hospital of Goettingen
  • Mannheim, Germany, D-68167
    • University hospital of Mannheim
  • Murnau, Germany, D-82418
    • BG-Unfallklinik Murnau
  • Siegen, Germany, D-57074
    • Ev. Jung-Stilling-Krankenhaus
  • Ulm, Germany, D-89070
    • Bundeswehrkrankenhaus Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult trauma patients presenting with presumed traumatic hemorrhagic shock (systolic arterial blood pressure <90 mm Hg) that does not respond to the first 10 min of standard shock treatment [endotracheal intubation, crystalloid-, colloid-, and hypertonic saline (up to 4 ml/kg) fluid resuscitation, and catecholamine (ephedrine, phenylephrine, norepinephrine, epinephrine) vasopressors].

Exclusion Criteria:

• Terminal illness
• No intravenous access
• Age < 18 years
• Injury > 60 min before randomization
• Known pregnancy
• Cardiac arrest before randomization
• Presence of a do-not-resuscitate order
• Untreated tension pneumothorax
• Untreated cardiac tamponade
• Participation in another clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vasopressin; Vasopressin, 10 I.U./4 ml, Solution for Injection	Drug: Vasopressin; 10 minutes after standard shock treatment 10 IU arginine vasopressin will be injected; if shock persists for 5 minutes, another 10 IU arginine vasopressin will be injected; after 5 minutes persisting shock, the last 10 IU arginine vasopressin will be injected; Total duration: approx. 15 minutes; Dose per intravenous injection: 10 IU; max. dose: 30 IU arginine vasopressin; Other Names: Pitressin; Pressyn; CPREssin
Placebo Comparator: Saline; Saline placebo 4 ml, Solution for Injection	Drug: Saline placebo; Placebo for arginine vasopressin; Other Names: Saline; Kochsalz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary end point will be hospital admission rate	time from trauma to hospital admission

Secondary Outcome Measures

Outcome Measure	Time Frame
Hemodynamic variables	time from trauma to hospital discharge
Fluid resuscitation requirements	time from trauma to hospital discharge
Hospital discharge rate	time from trauma to hospital discharge

Collaborators and Investigators

• Sponsor: Volker Wenzel
• Investigators: Study Chair: Prof. Dr. Volker Wenzel, M.Sc., M.D., Innsbruck Medical University, Dep. for Anaesthesia and Crit. Care Management

Publications and helpful links

General Publications

• O'Callaghan DJ, Gordon AC. What's new in vasopressin? Intensive Care Med. 2015 Dec;41(12):2177-9. doi: 10.1007/s00134-015-3849-3. Epub 2015 May 7. No abstract available.
• Krismer AC, Wenzel V, Voelckel WG, Innerhofer P, Stadlbauer KH, Haas T, Pavlic M, Sparr HJ, Lindner KH, Koenigsrainer A. Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock. Three cases and a brief analysis of the literature. Anaesthesist. 2005 Mar;54(3):220-4. doi: 10.1007/s00101-004-0793-y.
• Schummer W, Schummer C, Fuchs J. [Vasopressin]. Anaesthesist. 2005 Jul;54(7):707-8. doi: 10.1007/s00101-005-0854-x. No abstract available. German.
• Tsuneyoshi I, Onomoto M, Yonetani A, Kanmura Y. Low-dose vasopressin infusion in patients with severe vasodilatory hypotension after prolonged hemorrhage during general anesthesia. J Anesth. 2005;19(2):170-3. doi: 10.1007/s00540-004-0299-4.
• Raedler C, Voelckel WG, Wenzel V, Krismer AC, Schmittinger CA, Herff H, Mayr VD, Stadlbauer KH, Lindner KH, Konigsrainer A. Treatment of uncontrolled hemorrhagic shock after liver trauma: fatal effects of fluid resuscitation versus improved outcome after vasopressin. Anesth Analg. 2004 Jun;98(6):1759-1766. doi: 10.1213/01.ANE.0000117150.29361.5A.
• Stadlbauer KH, Wenzel V, Krismer AC, Voelckel WG, Lindner KH. Vasopressin during uncontrolled hemorrhagic shock: less bleeding below the diaphragm, more perfusion above. Anesth Analg. 2005 Sep;101(3):830-832. doi: 10.1213/01.ANE.0000175217.55775.1C. No abstract available.
• Stadlbauer KH, Wagner-Berger HG, Raedler C, Voelckel WG, Wenzel V, Krismer AC, Klima G, Rheinberger K, Nussbaumer W, Pressmar D, Lindner KH, Konigsrainer A. Vasopressin, but not fluid resuscitation, enhances survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. Anesthesiology. 2003 Mar;98(3):699-704. doi: 10.1097/00000542-200303000-00018.
• Voelckel WG, Raedler C, Wenzel V, Lindner KH, Krismer AC, Schmittinger CA, Herff H, Rheinberger K, Konigsrainer A. Arginine vasopressin, but not epinephrine, improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs. Crit Care Med. 2003 Apr;31(4):1160-5. doi: 10.1097/01.CCM.0000060014.75282.69.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: September 21, 2006
• First Submitted That Met QC Criteria: September 21, 2006
• First Posted (Estimate): September 22, 2006

Study Record Updates

• Last Update Posted (Estimate): November 5, 2014
• Last Update Submitted That Met QC Criteria: November 4, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: shock; vasopressin; traumatic; hemorrhagic; Hypovolemic Shock; shock treatment; Circulatory Collapse
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Shock; Shock, Hemorrhagic; Hypovolemia; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: Vitris